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The role of miR-92b-3p in notch signaling and monitoring of oral squamous cell carcinoma

Oncogene volume 44, pages 1300–1311 (2025)Cite this article

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Abstract

Dysregulation of microRNAs (miRNAs) influences diverse hallmarks of cancer, including proliferative signaling, metastasis, and resistance to cell death. We explored the contribution of miR-92b-3p in oral squamous cell carcinoma (OSCC) and its potential as a monitoring biomarker. Analysis of TCGA, GEO, and our own cohort revealed dysregulation of miR-92b-3p in OSCC, which correlated with aggressive tumor characteristics. miR-92b-3p overexpression augmented proliferation and the epithelial-mesenchymal transition in both YD8 and SCC25 cell lines and xenograft models. Mechanically, augmented miR-92b-3p expression suppressed ATXN1 and CPEB3, activating the Notch signaling pathway and thereby promoting metastasis and cisplatin resistance. In our cohort, serum miR-92b-3p expression reflected the disease status, including relapse. Our results suggest that miR-92b-3p might be an onco-miR involved in OSCC through regulating the ATXN1/CPEB3/Notch pathway. These findings provide novel insights for treating and monitoring OSCC.

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Fig. 1: Elevated miR-92b-3p levels are associated with worse progression of oral squamous cell carcinoma (OSCC).
Fig. 2: ATXN1 and CPEB3 attenuate miR-92b-3p–mediated promotion of aggressiveness in oral squamous cell carcinoma (OSCC).
Fig. 3: miR-92b-3p/ATXN1/CPEB3 interactions regulate OSCC cell proliferation and metastasis via the Notch signaling pathways.
Fig. 4: miR-92b-3p promotes cell growth and metastasis in oral squamous cell carcinoma (OSCC) in vivo.
Fig. 5: Upregulation of miR-92b-3p increases tumorigenesis and resistance to cisplatin-based therapy in OSCC.
Fig. 6: Circulating levels of miR-92b-3p are related to the tumor burden in patients with OSCC.

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Data availability

The TCGA data presented in this study are openly available in a specific portal (https://tcga-data.nci.nih.gov) and cancer browser (https://genome-cancer.ucsc.edu). The GSE45238 and GSE168227 datasets were acquired from the Gene Expression Omnibus database (http://www.ncbi.nlm.nih.gov/geo/). Further information is available from the corresponding author upon request.

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Funding

This research was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning [grant numbers RS-2024-00339029 to BS Koo and 2022R1C1C1008265 to HR Won], and by the Korea Health Technology R&D Project through the Korea health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HR22C1734).

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Author notes

  1. These authors contributed equally: Ho-Ryun Won, Bon Seok Koo.

Authors and Affiliations

  1. Dental Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qingchun Road, Hangzhou, 310016, Zhejiang, China

    Yudan Piao

  2. Department of Medical Science, Chungnam National University College of Medicine, Daejeon, Republic of Korea

    Yudan Piao, Sicong Zheng, Chan Oh, Yan Li Jin, Shan Shen, Quoc Khanh Nguyen, Se-Hee Park, Jae Won Chang, Ho-Ryun Won & Bon Seok Koo

  3. Department of Otolaryngology-Head and Neck Surgery, Chungnam National University College of Medicine, Daejeon, Republic of Korea

    Seung-Nam Jung, Mi Ae Lim, Jae Won Chang, Ho-Ryun Won & Bon Seok Koo

  4. Radiation Oncology, Chungnam National University Sejong Hospital, Daejeon, Republic of Korea

    Young il Kim

  5. Department of Otorhinolaryngology-Head and Neck Surgery, Chungnam National University Hospital, Daejeon, Republic of Korea

    Min-Gyu Kim

  6. Department of Otorhinolaryngology-Head and Neck Surgery, Chungnam National University Sejong Hospital, Sejong, Republic of Korea

    Ji Won Kim

  7. Department of Biology, Temple University, Philadelpha, PA, 19122, USA

    Sun Ohm

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Contributions

The work reported in the paper has been performed by the authors, unless clearly specified in the text. YP, contributed to conception, design, data acquisition, and interpretation, drafted and critically revised the manuscript; SNJ, MAL, JWC, MGK, JWK and SZ contributed to design and data acquisition, CO, NQK, SS, YLJ, SP, SO and YK contributed to data analysis; HRW and BSK contributed to conception, design and critically revised the manuscript. All authors gave final approval and agree to be accountable for all aspects of the work.

Corresponding authors

Correspondence to Ho-Ryun Won or Bon Seok Koo.

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The authors declare no competing interests.

Ethics approval and consent to participate

This study was conducted with signed informed consent under the approval and guidance of the Ethics Review Board of Chungnam National University Hospital (CNUH-2022-11-004-001). All experiments adhered to the relevant guidelines and regulations of the animal care unit at Chungnam National University. The animal protocols for these experiments received approval from the Ethics Committee of Animal Experimentation of Chungnam National University (No. CNUH-2022-IA0100-00).

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Piao, Y., Jung, SN., Lim, M.A. et al. The role of miR-92b-3p in notch signaling and monitoring of oral squamous cell carcinoma. Oncogene 44, 1300–1311 (2025). https://doi.org/10.1038/s41388-025-03306-2

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